Allele Interaction – Single Locus Genetics Meets Regulatory Biology

Background: Since the dawn of genetics, additive and dominant gene action in diploids have been defined by comparison of heterozygote and homozygote phenotypes. However, these definitions provide little insight into the underlying intralocus allelic functional dependency and thus cannot serve directly as a mediator between genetics theory and regulatory biology, a link that is sorely needed. Methodology/Principal Findings: We provide such a link by distinguishing between positive, negative and zero allele interaction at the genotype level. First, these distinctions disclose that a biallelic locus can display 18 qualitatively different allele interaction sign motifs (triplets of +, – and 0). Second, we show that for a single locus, Mendelian dominance is not related to heterozygote allele interaction alone, but is actually a function of the degrees of allele interaction in all the three genotypes. Third, we demonstrate how the allele interaction in each genotype is directly quantifiable in gene regulatory models, and that there is a unique, one-to-one correspondence between the sign of autoregulatory feedback loops and the sign of the allele interactions. Conclusion/Significance: The concept of allele interaction refines single locus genetics substantially, and it provides a direct link between classical models of gene action and gene regulatory biology. Together with available empirical data, our results indicate that allele interaction can be exploited experimentally to identify and explain intricate intra- and inter-locu

Tracking aftershock sequences using empirical matched field processing

Extensive aftershock sequences present a significant problem to seismological data centres attempting to produce near real-time comprehensive seismic event bulletins. An elevated number of events to process and poorer performance of automatic phase association algorithms can lead to large delays in processing and a greatly increased human workload. Global monitoring is often performed using seismic array stations at considerable distances from the events involved. Empirical matched field processing (EMFP) is a narrow-frequency band array signal processing technique that recognizes the inter-sensor phase and amplitude relations associated with wavefronts approaching a sensor array from a given direction. We demonstrate that EMFP, using a template obtained from the first P arrival from the main shock alone, can efficiently detect and identify P arrivals on that array from subsequent events in the aftershock zone with exceptionally few false alarms (signals from other sources). The empirical wavefield template encodes all the narrow-band phase and amplitude relations observed for the main shock signal. These relations are also often robust and repeatable characteristics of signals from nearby events. The EMFP detection statistic compares the phase and amplitude relations at a given time in the incoming data stream with those for the template and is sensitive to very short-duration signals with the required characteristics. Significant deviations from the plane-wavefront model that typically degrade the performance of standard beamforming techniques can enhance signal characterization using EMFP. Waveform correlation techniques typically perform poorly for aftershocks from large earthquakes due to the distances between hypocentres and the wide range of event magnitudes and source mechanisms. EMFP on remote seismic arrays mitigates these difficulties; the narrow-band nature of the procedure makes arrival identification less sensitive to the signals’ temporal form and spectral content. The empirical steering vectors derived for the main shock P arrival can reduce the frequency dependency of the slowness vector estimates. This property helps us to automatically screen out arrivals from outside of the aftershock zone. Standard array processing pipelines could be enhanced by including both plane-wave and empirical matched field steering vectors. This would maintain present capability for the plane-wave steering vectors and provide increased sensitivity and resolution for those sources for which we have empirical calibrations.Tracking aftershock sequences using empirical matched field processingacceptedVersio

PERANCANGAN ALAT PENJEJAK MATAHARI PADA APLIKASI PEMBANGKIT LISTRIK TENAGA SURYA

Penggunaan panel sel surya sebagai sumber energi utama sudah banyak dikembangkan a ikasi industri maupun pada aplikasi rumah tangga. Namun penggunaan panel sel surya tersebut lebih banyak difokuskan sebagai sumber energi terbarukan dan ramah lingkungan. Penelitian-penelitian untuk mengkaji bagaimana mengefisiensikan penggunaan panel surya sebagai surnber energi utama belum banyak dilakukan. Penelitian ini mengkaji bagaimana mengefisiensikan penggunaan panel sel surya melalui rangkaian sistem alat yang disebut alat penjejak matahari. _Alat penjejak matahari yang akan dirancang menggunakan sensor LDR sebagai komponen deteksi arah pergerakan matahari yang dikendalikan secara otomatis oleh mikro konntroller AVR Atmega 2560. Hasil pengujian menunjukkan penggunaan rancangan alat penjajak matahari dapat meningkatkan rata-rata proseniase tegangan keluaran sel surya bisa mencapai 188% bila dibandingkan dengan kondisi sebelum panel sel surya menggunakan sistem alat penjajak matahar

The European Plate Observing System and the Arctic

The European Plate Observing System (EPOS) aims to integrate existing infrastructures in the solid earth sciences into a single infrastructure, enabling earth scientists across Europe to combine, model, and interpret multidisciplinary datasets at different time and length scales. In particular, a primary objective is to integrate existing research infrastructures within the fields of seismology, geodesy, geophysics, geology, rock physics, and volcanology at a pan-European level. The added value of such integration is not visible through individual analyses of data from each research infrastructure; it needs to be understood in a long-term perspective that includes the time when changes implied by current scientific research results are fully realized and their societal impacts have become clear. EPOS is now entering its implementation phase following a four-year preparatory phase during which 18 member countries in Europe contributed more than 250 research infrastructures to the building of this pan-European vision. The Arctic covers a significant portion of the European plate and therefore plays an important part in research on the solid earth in Europe. However, the work environment in the Arctic is challenging. First, most of the European Plate boundary in the Arctic is offshore, and hence, sub-sea networks must be built for solid earth observation. Second, ice covers the Arctic Ocean where the European Plate boundary crosses through the Gakkel Ridge, so innovative technologies are needed to monitor solid earth deformation. Therefore, research collaboration with other disciplines such as physical oceanography, marine acoustics, and geo-biology is necessary. The establishment of efficient research infrastructures suitable for these challenging conditions is essential both to reduce costs and to stimulate multidisciplinary research.Le système European Plate Observing System (EPOS) vise l’intégration des infrastructures actuelles en sciences de la croûte terrestre afin de ne former qu’une seule infrastructure pour que les spécialistes des sciences de la Terre des quatre coins de l’Europe puissent combiner, modéliser et interpréter des ensembles de données multidisciplinaires moyennant diverses échelles de temps et de longueur. Un des principaux objectifs consiste plus particulièrement à intégrer les infrastructures de recherche existantes se rapportant aux domaines de la sismologie, de la géodésie, de la géophysique, de la géologie, de la physique des roches et de la volcanologie à l’échelle paneuropéenne. La valeur ajoutée de cette intégration n’est pas visible au moyen des analyses individuelles des données émanant de chaque infrastructure de recherche. Elle doit plutôt être considérée à la lumière d’une perspective à long terme, lorsque les changements qu’impliquent les résultats de recherche scientifique actuels auront été entièrement réalisés et que les incidences sur la société seront claires. Le système EPOS est en train d’amorcer sa phase de mise en oeuvre. Cette phase succède à la phase préparatoire de quatre ans pendant laquelle 18 pays membres de l’Europe ont soumis plus de 250 infrastructures de recherche en vue de l’édification de cette vision paneuropéenne. L’Arctique couvre une grande partie de la plaque européenne et par conséquent, il joue un rôle important dans les travaux de recherche portant sur la croûte terrestre en Europe. Cependant, le milieu de travail de l’Arctique n’est pas sans défis. Premièrement, la majorité de la limite de la plaque européenne se trouvant dans l’Arctique est située au large, ce qui signifie que des réseaux marins doivent être aménagés pour permettre l’observation de la croûte terrestre. Deuxièmement, de la glace recouvre l’océan Arctique, là où la limite de la plaque européenne traverse la dorsale de Gakkel, ce qui signifie qu’il faut recourir à des technologies innovatrices pour surveiller la déformation de la croûte terrestre. C’est pourquoi les travaux de recherche doivent nécessairement se faire en collaboration avec d’autres disciplines comme l’océanographie physique, l’acoustique marine et la géobiologie. L’établissement d’infrastructures de recherche efficaces capables de faire face à ces conditions rigoureuses s’avère essentiel, tant pour réduire les coûts que pour stimuler la recherche multidisciplinaire

Real time optical immunosensing with flow-through porous alumina membranes

Through the presentation of analytical data from bioassay experiments, measured by polarimetry, we demonstrate for the first time a real time immunoassay within a free standing macroporous alumina membrane. The 200 nm nominal pore diameter of the membrane enables flow-through, thereby providing an ideal fluidic platform for the targeted delivery of analytes to bioreceptors immobilized on the pore walls, enabling fast sensing response times and the use of small sample volumes (<100 μL). For the immunoassay, the pore walls were first coated with the functional copolymer, copoly(DMA-NAS) using a novel coupling process, before immobilization of the allergen protein, β-lactoglobulin, by spotting. The immuno-assay then proceeded with the binding of the primary and secondary antibody cognates, rabbit anti-β-lactoglobulin and anti-rabbit IgG respectively. Through the use of streptavidin coated quantum dots as refractive index signal enhancers, a noise floor for individual measurements of 3.7 ng/mL (25 pM) was obtained, with an overall statistical, or formal assay LOD of 33.7 ng/mL (225 pM), for total assay time below 1 h

Casein SNP in Norwegian goats: additive and dominance effects on milk composition and quality

<p>Abstract</p> <p>Background</p> <p>The four casein proteins in goat milk are encoded by four closely linked casein loci (<it>CSN1S1</it>, <it>CSN2</it>, <it>CSN1S2 </it>and <it>CSN3</it>) within 250 kb on caprine chromosome 6. A deletion in exon 12 of <it>CSN1S1</it>, so far reported only in Norwegian goats, has been found at high frequency (0.73). Such a high frequency is difficult to explain because the national breeding goal selects against the variant's effect.</p> <p>Methods</p> <p>In this study, 575 goats were genotyped for 38 Single Nucleotide Polymorphisms (SNP) located within the four casein genes. Milk production records of these goats were obtained from the Norwegian Dairy Goat Control. Test-day mixed models with additive and dominance fixed effects of single SNP were fitted in a model including polygenic effects.</p> <p>Results</p> <p>Significant additive effects of single SNP within <it>CSN1S1 </it>and <it>CSN3 </it>were found for fat % and protein %, milk yield and milk taste. The allele with the deletion showed additive and dominance effects on protein % and fat %, and overdominance effects on milk quantity (kg) and lactose %. At its current frequency, the observed dominance (overdominance) effects of the deletion allele reduced its substitution effect (and additive genetic variance available for selection) in the population substantially.</p> <p>Conclusions</p> <p>The selection pressure of conventional breeding on the allele with the deletion is limited due to the observed dominance (overdominance) effects. Inclusion of molecular information in the national breeding scheme will reduce the frequency of this deletion in the population.</p

Factors associated with non-attendance, opportunistic attendance and reminded attendance to cervical screening in an organized screening program: a cross-sectional study of 12,058 Norwegian women

<p>Abstract</p> <p>Background</p> <p>Cervical cancer incidence and mortality may be reduced by organized screening. Participant compliance with the attendance recommendations of the screening program is necessary to achieve this. Knowledge about the predictors of compliance is needed in order to enhance screening attendance.</p> <p>Methods</p> <p>The Norwegian Co-ordinated Cervical Cancer Screening Program (NCCSP) registers all cervix cytology diagnoses in Norway and individually reminds women who have no registered smear for the past three years to make an appointment for screening. In the present study, a questionnaire on lifestyle and health was administered to a random sample of Norwegian women. The response rate was 68%. To address the predictors of screening attendance for the 12,058 women aged 25-45 who were eligible for this study, individual questionnaire data was linked to the cytology registry of the NCCSP. We distinguished between non-attendees, opportunistic attendees and reminded attendees to screening for a period of four years. Predictors of non-attendance versus attendance and reminded versus opportunistic attendance were established by multivariate logistic regression.</p> <p>Results</p> <p>Women who attended screening were more likely than non-attendees to report that they were aware of the recommended screening interval, a history of sexually transmitted infections and a history of hormonal contraceptive and condom use. Attendance was also positively associated with being married/cohabiting, being a non-smoker and giving birth. Women who attended after being reminded were more likely than opportunistic attendees to be aware of cervical cancer and the recommended screening interval, but less likely to report a history of sexually transmitted infections and hormonal contraceptive use. Moreover, the likelihood of reminded attendance increased with age. Educational level did not significantly affect the women's attendance status in the fully adjusted models.</p> <p>Conclusions</p> <p>The likelihood of attendance in an organized screening program was higher among women who were aware of cervical screening, which suggests a potential for a higher attendance rate through improving the public knowledge of screening. Further, the lower awareness among opportunistic than reminded attendees suggests that physicians may inform their patients better when smears are taken at the physician's initiative.</p

Fourteen sequence variants that associate with multiple sclerosis discovered by meta-analysis informed by genetic correlations

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesA meta-analysis of publicly available summary statistics on multiple sclerosis combined with three Nordic multiple sclerosis cohorts (21,079 cases, 371,198 controls) revealed seven sequence variants associating with multiple sclerosis, not reported previously. Using polygenic risk scores based on public summary statistics of variants outside the major histocompatibility complex region we quantified genetic overlap between common autoimmune diseases in Icelanders and identified disease clusters characterized by autoantibody presence/absence. As multiple sclerosis-polygenic risk scores captures the risk of primary biliary cirrhosis and vice versa (P = 1.6 x 10(-7), 4.3 x 10(-9)) we used primary biliary cirrhosis as a proxy-phenotype for multiple sclerosis, the idea being that variants conferring risk of primary biliary cirrhosis have a prior probability of conferring risk of multiple sclerosis. We tested 255 variants forming the primary biliary cirrhosis-polygenic risk score and found seven multiple sclerosis-associating variants not correlated with any previously established multiple sclerosis variants. Most of the variants discovered are close to or within immune-related genes. One is a low-frequency missense variant in TYK2, another is a missense variant in MTHFR that reduces the function of the encoded enzyme affecting methionine metabolism, reported to be dysregulated in multiple sclerosis brain.Swedish Research Council Knut and Alice Wallenberg Foundation AFA Foundation Swedish Brain Foundatio

Determination of c-myc amplification and overexpression in breast cancer patients: evaluation of its prognostic value against c-erbB-2, cathepsin-D and clinicopathological characteristics using univariate and multivariate analysis

C-myc and c-erbB-2 amplification and/or overexpression as well as total cathepsin-D (CD) concentration have been reported to be associated with poor prognosis in breast cancer. The prognostic significance, however, remains somewhat controversial, partly because of discrepancies among the different methodologies used. We determined the amplification and overexpression of c-myc oncogene in 152 breast cancer patients and examined its prognostic value in relation to c-erbB-2 amplification and overexpression, high concentration of CD (≥ 60 pmol mg–1 protein) and standard clinicopathological prognostic factors of the disease. High CD concentration, as well as c-myc amplification and overexpression, proved to be the best of the new variables examined for prediction of early relapse (ER; before 3 years). After multivariate analysis only CD remained significant, which suggests that the prognostic power of these variables is similar. Using univariate analysis we proved that c-myc amplification and overexpression were highly significant for disease-free survival (DFS) (P = 0.0016 and P = 0.0001 respectively) and overall survival (OS) (P < 0.0001 and P = 0.0095 respectively), although by multivariate analysis c-myc overexpression was statistically significant only for DFS (P = 0.0001) and c-myc amplification only for OS (P = 0.0006). With regard to c-erbB-2, only its overexpression appeared to be significant for DFS and OS, although after multivariate analysis its prognostic power was weaker (P = 0.030 and P = 0.024 respectively). c-myc amplification and overexpression exhibited a tendency for locoregional recurrence (LRR) (P = 0.0024 and P = 0.0075 respectively), however, their prognostic value was lower after multivariate analysis and only CD remained significant. © 1999 Cancer Research Campaig

Fourteen sequence variants that associate with multiple sclerosis discovered by meta-analysis informed by genetic correlations

A meta-analysis of publicly available summary statistics on multiple sclerosis combined with three Nordic multiple sclerosis cohorts (21,079 cases, 371,198 controls) revealed seven sequence variants associating with multiple sclerosis, not reported previously. Using polygenic risk scores based on public summary statistics of variants outside the major histocompatibility complex region we quantified genetic overlap between common autoimmune diseases in Icelanders and identified disease clusters characterized by autoantibody presence/absence. As multiple sclerosis-polygenic risk scores captures the risk of primary biliary cirrhosis and vice versa (P = 1.6 x 10(-7), 4.3 x 10(-9)) we used primary biliary cirrhosis as a proxy-phenotype for multiple sclerosis, the idea being that variants conferring risk of primary biliary cirrhosis have a prior probability of conferring risk of multiple sclerosis. We tested 255 variants forming the primary biliary cirrhosis-polygenic risk score and found seven multiple sclerosis-associating variants not correlated with any previously established multiple sclerosis variants. Most of the variants discovered are close to or within immune-related genes. One is a low-frequency missense variant in TYK2, another is a missense variant in MTHFR that reduces the function of the encoded enzyme affecting methionine metabolism, reported to be dysregulated in multiple sclerosis brain.publishedVersio